Alterations in the anandamide metabolism in the development of neuropathic pain.

Natalia Malek,Mateusz Kucharczyk,Katarzyna Starowicz

doi:10.1155/2014/686908

Natalia Malek, Mateusz Kucharczyk + Show 1 more

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https://doi.org/10.1155/2014/686908

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Abstract

Endocannabinoids (EC), particularly anandamide (AEA), released constitutively in pain pathways might be accountable for the inhibitory effect on nociceptors. Pathogenesis of neuropathic pain may reflect complex remodeling of the dorsal root ganglia (DRGs) and spinal cord EC system. Multiple pathways involved both in the biosynthesis and degradation of AEA have been suggested. We investigated the local synthesis and degradation features of AEA in DRGs and spinal cord during the development and maintenance of pain in a model of chronic constriction injury (CCI). All AEA synthesis and degradation enzymes are present on the mRNA level in DRGs and lumbar spinal cord of intact as well as CCI-treated animals. Deregulation of EC system components was consistent with development of pain phenotype at days 3, 7, and 14 after CCI. The expression levels of enzymes involved in AEA degradation was significantly upregulated ipsilateral in DRGs and spinal cord at different time points. Expression of enzymes of the alternative, sPLA2-dependent and PLC-dependent, AEA synthesis pathways was elevated in both of the analyzed structures at all time points. Our data have shown an alteration of alternative AEA synthesis and degradation pathways, which might contribute to the variation of AEA levels and neuropathic pain development.

Highlights

The development of neuropathic pain after nerve injury occurs when peripheral nerve fibers are damaged or dysfunctional, which results in incorrect signals being sent to the brain and loss of afferent sensory function with typical features such as allodynia and hyperalgesia [1, 2]
Rats Subjected to constriction injury (CCI) Showed Signs of Allodynia on the Operated Paw at 3, 7, and 14 Days after Induction of Injury
Given the importance of the first-order neurons located in the DRGs and the spinal cord for pain sensation, in the present study, we investigated the putative AEA synthesizing and degradation enzymatic pathways in those structures

Summary

Introduction

The development of neuropathic pain after nerve injury occurs when peripheral nerve fibers are damaged or dysfunctional, which results in incorrect signals being sent to the brain and loss of afferent sensory function with typical features such as allodynia and hyperalgesia [1, 2]. Among the many suggested strategies to treat neuropathic pain, cannabinoids have the potential to become analgesic targets for drug development. Cannabinoid agonists suppress neuropathic symptoms in animal models of neuropathic pain evoked by chronic constriction injury (CCI) to the sciatic nerve [4,5,6] or spinal nerve ligation [7,8,9,10]. This therapeutic intervention is associated with a number of adverse effects, including sedation, motor impairment, and cognitive impairment. Anandamide (AEA), the first discovered and best studied EC, acts via cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors in a manner similar to naturally derived and synthetic cannabinoid agonists, but it may modulate nociception via other receptors, that is, transient receptor potential vanilloid 1 (TRPV1) [15,16,17,18]

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